Presently surgery is the most effective way to obtain a controlled weight reduction in morbidly obese patients. Roux-en-Y gastric bypass (RYGBP) surgery is effective and used worldwide, but the exact mechanism of action is unknown. The effect of RYGBP on ghrelin, insulin, adiponectin, and leptin levels was investigated in 66 obese subjects; mean weight 127 kg (range, 96-195 kg) and mean body mass index (BMI) 45 kg/m(2) (range, 33-64) before and after surgery. Ghrelin levels were also compared in 10 nonoperated and 10 operated obese, BMI-matched women. RYGBP resulted in 22% and 30% weight loss at 6 and 12 months, respectively. Ghrelin increased by 44% and 62% and adiponectin by 36% and 98%, but insulin declined by 57% and 62% and leptin by 60% and 64%. The changes were all related to the reduction in BMI. In addition, ghrelin and insulin were inversely correlated at all time points as were changes of the peptides at 12 months (F = 4.9, P = 0.031), independent of the change in BMI. No evidence for RYGBP surgery per se having an effect on ghrelin levels, independent of weight loss, was obtained. The profound changes in the regulatory peptides are likely to reflect the new state of energy balance achieved. A close inverse association between ghrelin and insulin was observed, supporting an important role for ghrelin in glucose homeostasis.

Ghrelin is a recently discovered gastric peptide that increases appetite, glucose oxidation, and lipogenesis and stimulates the secretion of GH. In contrast to ghrelin, GH promotes lipolysis, glucose production, and insulin secretion. Both ghrelin and GH are suppressed by intake of nutrients, especially glucose. The role of GH in the regulation of ghrelin has not yet been established. We investigated the effect of GH on circulating levels of ghrelin in relation to its effects on glucose, insulin, body composition, and the adipocyte-derived peptides leptin and adiponectin. Thirty-six patients with adult-onset GH deficiency received recombinant human GH for 9 months in a placebo-controlled study. Body composition and fasting serum analytes were assessed at baseline and at the end of the study. The GH treatment was accompanied by increased serum levels of IGF-I, reduced body weight (-2%) and body fat (-27%), and increased serum concentrations of glucose (+10%) and insulin (+48%). Ghrelin levels decreased in 30 of 36 subjects by a mean of -29%, and leptin decreased by a mean of -24%. Adiponectin increased in the women only. The decreases in ghrelin and leptin correlated with changes in fat mass, fat-free mass, and IGF-I. The reductions in ghrelin were predicted independently of the changes in IGF-I and fat mass. It is likely that the reductions in ghrelin and leptin reflect the metabolic effects of GH on lipid mobilization and glucose production. Possibly, a suppression of ghrelin promotes loss of body fat in GH-deficient patients receiving treatment. The observed correlation between the changes in ghrelin and IGF-I may suggest that the GH/IGF-I axis has a negative feedback on ghrelin secretion.

OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m 2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m 2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r ¼ À0.36, P ¼ 0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4 (insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

Ghrelin and PP fall transiently after surgery, possibly due to vagal dysfunction, and ultimately, as weight loss ensues, ghrelin secretion increases to higher than preoperative levels. The RYBGP procedure affects the gastric mucosa, as reflected by a transient increase in circulating PGI, and subsequently, the mucosa in the excluded stomach is at rest, as shown by low levels of PGI and gastrin.

Objective: Overfeeding suppresses GH secretion and makes evaluation of a suspected GH deficiency (GHD) difficult. In normal weight subjects, gender is known to influence GH concentrations, which is most apparent in the ambulatory, morning-fasted state. In this study, we examined the GH/IGF-I axis in obese men and women and the effect of surgically induced weight loss. Design: Sixty-three subjects (body mass index (BMI) 45^6 kg/m 2 ; 54 women, 9 men) were studied prior to, and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. Fifty-four patients with classic GHD (BMI 27^6 kg/m 2 ; 35 men, 19 women) were included for comparison. Methods: Hormones were analysed in fasting morning serum samples. Results: RYGBP resulted in a decreased BMI to 35^kg/m 2 at 6 months and 32^6 kg/m 2 at 12 months. GH and IGF-I increased at 6 months in the women and at 12 months in both sexes by $ 300 and 11% respectively. Prior to RYGBP, GH concentrations were low in the obese men and similar to those of GHD men (mean 0.09 mU/l). Obese women had tenfold higher values than obese men and sevenfold higher than GHD women. IGF-I levels were in the low reference range in the obese and below 22 S.D. for age in 13%. Conclusions: Surgically induced weight loss partially restores GH secretion. Despite a marked suppression of GH values, a gender influence is maintained in severe obesity. In obese women, single morning GH and IGF-I values seem sufficient to exclude a suspicion of classic GHD.European Journal of Endocrinology 154 53-59

Objective: The marked weight loss induced by Roux-en-Y gastric bypass (RYGBP) for morbid obesity is still incompletely understood. It has been suggested that, besides the restriction imposed by the surgical procedure, alterations in gut regulatory peptides signaling the brain might contribute. The aim of this study was to measure the putative satiety peptides peptide YY (PYY), glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP) and pro-neurotensin (pro-NT) in response to fasting and feeding. Design: The study is a cross-sectional study. After a prolonged overnight 14 h fast, a standardized mixed meal (574 kcal) was provided. Blood samples for peptide measurements were obtained before and after the meal. Subjects: Forty subjects (20 males and females) were included; 10 morbidly obese; (mean age 41 ± 7 years; mean BMI 44 ± 3 kg/m 2 ), 10 operated with RYGBP (age 45 ± 5 years; BMI 35 ± 6 kg/m 2 ), 10 aged-matched lean (age 44 ± 5 years; BMI 24 ± 3 kg/m 2 ) and 10 young lean subjects (age 26 ± 2 years; BMI 23 ± 2 kg/m 2 ). Measurements: Plasma concentrations of PYY, GLP-1, PP and pro-NT were obtained. Results: PYY levels increased more in the RYGBP group than in the other groups after the test meal. GLP-1 levels rose in the RYGBP patients, with a small increase seen in the age-matched lean group. PP concentrations increased similarly in all groups postprandially. Pro-NT levels were highest in surgical patients, with no meal effect. Conclusion: RYGBP subjects displayed exaggerated PYY and GLP-1 responses to a standardized meal and demonstrated higher pro-NT levels both pre-and postprandially. The findings indicate that possibly the alterations in gut peptide secretion may promote weight loss after gastric bypass surgery.

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